PubMed

Planta Med. 2024 Jun;90(7-08):512-522. doi: 10.1055/a-2192-3167. Epub 2024 Jun 6.ABSTRACTThe use of Drosophila melanogaster as a biological platform to study the effect of diet and food bioactives on the metabolome remains a highly unexplored subject. Aiming to establish alternative solutions for the investigation of nutritional interventions with bioactive natural products by employing LC-MS-based metabolomics approaches, we assessed the effect of a phytonutrient-rich extract from the endemic Mediterranean plant Cichorium spinosum (stamnagkàthi) on a Drosophila population. The extract's modulating effect on the proteostasis network and metabolism of young D. melanogaster flies was evaluated. Furthermore, an untargeted metabolomics approach, employing a C18 UPLC-ESI-Orbitrap-HRMS/MS platform, permitted the detection of several biomarkers in the metabolic profile of Drosophila's tissues; while targeted amino acid quantification in Drosophila tissue was simultaneously performed by employing aTRAQ labeling and an ion-pairing UPLC-ESI-SWATH-HRMS/MS platform. The detected metabolites belong to different chemical classes, and statistical analysis with chemometrics tools was utilized to reveal patterns and trends, as well as to uncover potential class-distinguishing features and possible biomarkers. Our findings suggest that Drosophila can serve as a valuable in vivo model for investigating the role of bioactive phytoconstituents, like those found in C. spinosum's decoction, on diverse metabolic processes. Additionally, the fruit fly represents a highly effective platform to investigate the molecular mechanisms underlying sex differences in diverse aspects of nutrition and physiology in higher metazoans.PMID:38843791 | DOI:10.1055/a-2192-3167

Redox Biol. 2024 Jun 4;73:103222. doi: 10.1016/j.redox.2024.103222. Online ahead of print.ABSTRACTBACKGROUND: Cystathionine β-synthase (CBS)-deficient homocystinuria (HCU) is an inherited disorder of sulfur amino acid metabolism with varying severity and organ complications, and a limited knowledge about underlying pathophysiological processes. Here we aimed at getting an in-depth insight into disease mechanisms using a transgenic mouse model of HCU (I278T).METHODS: We assessed metabolic, proteomic and sphingolipidomic changes, and mitochondrial function in tissues and body fluids of I278T mice and WT controls. Furthermore, we evaluated the efficacy of methionine-restricted diet (MRD) in I278T mice.RESULTS: In WT mice, we observed a distinct tissue/body fluid compartmentalization of metabolites with up to six-orders of magnitude differences in concentrations among various organs. The I278T mice exhibited the anticipated metabolic imbalance with signs of an increased production of hydrogen sulfide and disturbed persulfidation of free aminothiols. HCU resulted in a significant dysregulation of liver proteome affecting biological oxidations, conjugation of compounds, and metabolism of amino acids, vitamins, cofactors and lipids. Liver sphingolipidomics indicated upregulation of the pro-proliferative sphingosine-1-phosphate signaling pathway. Liver mitochondrial function of HCU mice did not seem to be impaired compared to controls. MRD in I278T mice improved metabolic balance in all tissues and substantially reduced dysregulation of liver proteome.CONCLUSION: The study highlights distinct tissue compartmentalization of sulfur-related metabolites in normal mice, extensive metabolome, proteome and sphingolipidome disruptions in I278T mice, and the efficacy of MRD to alleviate some of the HCU-related biochemical abnormalities.PMID:38843767 | DOI:10.1016/j.redox.2024.103222

J Hazard Mater. 2024 May 28;474:134721. doi: 10.1016/j.jhazmat.2024.134721. Online ahead of print.ABSTRACTThe new challenges in toxicology demand novel and innovative in vitro approaches for deriving points of departure (PODs) and determining the mode of action (MOA) of chemicals. Therefore, the aim of this original study was to couple in vitro studies with untargeted metabolomics to model the concentration-response of extra- and intracellular metabolome data on human HepaRG cells treated for 48 h with three pyrrolizidine alkaloids (PAs): heliotrine, retrorsine and lasiocarpine. Modeling revealed that the three PAs induced various monotonic and, importantly, biphasic curves of metabolite content. Based on unannotated metabolites, the endometabolome was more sensitive than the exometabolome in terms of metabolomic effects, and benchmark concentrations (BMCs) confirmed that lasiocarpine was the most hepatotoxic PA. Regarding its MOA, impairment of lipid metabolism was highlighted at a very low BMC (first quartile, 0.003 µM). Moreover, results confirmed that lasiocarpine targets bile acids, as well as amino acid and steroid metabolisms. Analysis of the endometabolome, based on coupling concentration-response and PODs, gave encouraging results for ranking toxins according to their hepatotoxic effects. Therefore, this novel approach is a promising tool for next-generation risk assessment, readily applicable to a broad range of compounds and toxic endpoints.PMID:38843629 | DOI:10.1016/j.jhazmat.2024.134721

Clin Nutr. 2024 May 31;43(7):1725-1735. doi: 10.1016/j.clnu.2024.05.043. Online ahead of print.ABSTRACTBACKGROUND: Aging-related type 2 diabetes (T2DM) is characterized by hyperinsulinemia, insulin resistance, and β-cell dysfunction. However, the underlying molecular mechanisms remain to be unclear.METHODS: We conducted non-targeted metabolomics to compare human serum samples from young adults (YA), elderly adults (EA), and elderly adults with diabetes (EA + DM) of Chinese population. Adult mice and aged mice were intragastrically administered with varespladib every day for two weeks and metabolic characteristics were monitored. Serum levels of arachidonic acid, insulin, and C-peptide, as well as serum activity of secretory phospholipase A2 (sPLA2) were detected in mice. Mouse islet perfusion assays were used to assess insulin secretion ability. Phosphorylated AKT levels were measured to evaluate insulin sensitivities of peripheral tissues in mice.RESULTS: Non-targeted metabolomics analysis of human serum samples revealed differential metabolic signatures among the YA, EA, and EA + DM groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis revealed significant enhancement of arachidonic acid metabolism and glycerophospholipid metabolism in the EA group compared with the YA group. Further analysis identified two metabolic fluxes that favored the accumulation of arachidonic acid in the elderly. Increased levels of arachidonic acid were also confirmed in aged mice with hyperinsulinemia and insulin resistance, together with subsequent glucose intolerance. Conversely, inhibiting the generation of arachidonic acid with varespladib, an inhibitor of sPLA2, reduced aging-associated diabetes by improving hyperinsulinemia and hepatic insulin resistance in aged mice but not in adult mice. Islet perfusion assays also showed that varespladib treatment suppressed the enhanced insulin secretion observed in aged islets.CONCLUSIONS: Collectively, our findings uncover that arachidonic acid serves as a metabolic hub in Chinese elderly population. Our results also suggest that arachidonic acid plays a fundamental role in regulating β-cell function during aging and point to a novel therapy for aging-associated diabetes.PMID:38843581 | DOI:10.1016/j.clnu.2024.05.043

PLoS Comput Biol. 2024 Jun 6;20(6):e1011912. doi: 10.1371/journal.pcbi.1011912. Online ahead of print.ABSTRACTTo standardize metabolomics data analysis and facilitate future computational developments, it is essential to have a set of well-defined templates for common data structures. Here we describe a collection of data structures involved in metabolomics data processing and illustrate how they are utilized in a full-featured Python-centric pipeline. We demonstrate the performance of the pipeline, and the details in annotation and quality control using large-scale LC-MS metabolomics and lipidomics data and LC-MS/MS data. Multiple previously published datasets are also reanalyzed to showcase its utility in biological data analysis. This pipeline allows users to streamline data processing, quality control, annotation, and standardization in an efficient and transparent manner. This work fills a major gap in the Python ecosystem for computational metabolomics.PMID:38843301 | DOI:10.1371/journal.pcbi.1011912

PLoS One. 2024 Jun 6;19(6):e0304503. doi: 10.1371/journal.pone.0304503. eCollection 2024.ABSTRACTDrought stress is a prominent abiotic factor that adversely influences the growth and development of Bupleurum chinense during its seedling stage, negatively impacting biomass and secondary metabolite production, thus affecting yield and quality. To investigate the molecular mechanism underlying the response of B. chinense seedlings under drought stress, this study employed comprehensive physiological, transcriptomic, and metabolomic analyses. The results revealed that under drought stress, the root soluble sugar and free proline content in B. chinense seedlings significantly increased, while the activities of SOD, POD, and CAT increased in the leaves. These findings indicate the presence of distinct response mechanisms in B. chinense to cope with drought stress. Integrated analysis further identified significant correlations between genes and metabolites related to amino acid biosynthesis in the leaves, as well as genes and metabolites associated with acetaldehyde and dicarboxylic acid metabolism. In the roots, genes and metabolites related to plant hormone signaling and the tricarboxylic acid (TCA) cycle showed significant correlations. These findings provide vital views into the molecular-level response mechanisms of B. chinense under drought stress. Moreover, this study establishes the groundwork for identifying drought-tolerant genes and breeding drought-resistant varieties, which could improve the drought tolerance of medicinal plants and have broader implications for agriculture and crop production in water-scarce areas.PMID:38843246 | DOI:10.1371/journal.pone.0304503

PLoS Med. 2024 Jun 6;21(6):e1004388. doi: 10.1371/journal.pmed.1004388. eCollection 2024 Jun.ABSTRACTBACKGROUND: Frozen embryo transfer (FET) has become a widely employed assisted reproductive technology technique. There have historically been concerns regarding the long-term metabolic safety of FET technology in offspring due to pregnancy-induced hypertension and large for gestational age, both of which are well-recognized factors for metabolic dysfunction of children. Therefore, we aimed to compare the metabolic profiles of children born after frozen versus fresh embryo transfer at 2 to 5 years of age.METHODS AND FINDINGS: This was a prospective cohort study. Using data from the "Assisted Reproductive Technology borned KIDs (ARTKID)," a birth cohort of offspring born from assisted reproductive technology at the Institute of Women, Children and Reproductive Health, Shandong University, China. We included 4,246 singletons born after FET (n = 2,181) and fresh embryo transfer (n = 2,065) enrolled between 2008 and 2019 and assessed the glucose and lipid variables until the age of 2 to 5 years. During a mean follow-up of 3.6 years, no significant differences were observed in fasting blood glucose, fasting insulin, Homeostatic Model Assessment of Insulin Resistance Index, total cholesterol, triglycerides, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol levels between offspring conceived by fresh and frozen embryo transfer in the crude model and adjusted model (adjusted for parental age, parental body mass index, parental education level, paternal smoking, parity, offspring age and sex). These results remained consistent across subgroup analyses considering offspring age, the stage of embryo transfer, and the mode of fertilization. Results from sensitivity analysis on children matched for age within the cohort remains the same. The main limitation of our study is the young age of the offspring.CONCLUSIONS: In this study, the impact of FET on glucose and lipid profiles during early childhood was comparable to fresh embryo transfer. Long-term studies are needed to evaluate the metabolic health of offspring born after FET.PMID:38843150 | DOI:10.1371/journal.pmed.1004388

Metab Brain Dis. 2024 Jun 6. doi: 10.1007/s11011-024-01363-2. Online ahead of print.ABSTRACTSubarachnoid hemorrhage (SAH) is a serious hemorrhagic event with high mortality and morbidity. Multiple injurious events produced by SAH can lead to a series of pathophysiologic processes in the hypothalamus that can severely impact patients' life. These pathophysiologic processes usually result in physiologic derangements and dysfunction of the brain and multiple organs. This dysfunction involved multiple dimensions of the genome and metabolome. In our study, we induced the SAH model in rats to obtain hypothalamic tissue and serum. The samples were subsequently analyzed by transcriptomics and metabolomics. Next, the functional enrichment analysis of the differentially expressed genes and metabolites were performed by GO and KEGG pathway analysis. Through transcriptomic analysis of hypothalamus samples, 263 up-regulated differential genes, and 207 down-regulated differential genes were identified in SAH groups compared to Sham groups. In the KEGG pathway analysis, a large number of differential genes were found to be enriched in IL-17 signaling pathway, PI3K-Akt signaling pathway, and bile secretion. Liquid chromatography-mass spectrometry metabolomics technology was conducted on the serum of SAH rats and identified 11 up-regulated and 26 down-regulated metabolites in positive ion model, and 1 up-regulated and 10 down-regulated metabolites in negative ion model. KEGG pathways analysis showed that differentially expressed metabolites were mainly enriched in pathways of bile secretion and primary bile acid biosynthesis. We systematically depicted the neuro- and metabolism-related biomolecular changes occurring in the hypothalamus after SAH by performing transcriptomics and metabolomics studies. These biomolecular changes may provide new insights into hypothalamus-induced metabolic changes and gene expression after SAH.PMID:38842661 | DOI:10.1007/s11011-024-01363-2

Graefes Arch Clin Exp Ophthalmol. 2024 Jun 6. doi: 10.1007/s00417-024-06538-2. Online ahead of print.ABSTRACTPURPOSE: To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies.METHODS: In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes.RESULTS: AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl β-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence.CONCLUSIONS: This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.PMID:38842593 | DOI:10.1007/s00417-024-06538-2

Chem Res Toxicol. 2024 Jun 6. doi: 10.1021/acs.chemrestox.4c00002. Online ahead of print.ABSTRACTBenchmark dose (BMD) modeling estimates the dose of a chemical that causes a perturbation from baseline. Transcriptional BMDs have been shown to be relatively consistent with apical end point BMDs, opening the door to using molecular BMDs to derive human health-based guidance values for chemical exposure. Metabolomics measures the responses of small-molecule endogenous metabolites to chemical exposure, complementing transcriptomics by characterizing downstream molecular phenotypes that are more closely associated with apical end points. The aim of this study was to apply BMD modeling to in vivo metabolomics data, to compare metabolic BMDs to both transcriptional and apical end point BMDs. This builds upon our previous application of transcriptomics and BMD modeling to a 5-day rat study of triphenyl phosphate (TPhP), applying metabolomics to the same archived tissues. Specifically, liver from rats exposed to five doses of TPhP was investigated using liquid chromatography-mass spectrometry and 1H nuclear magnetic resonance spectroscopy-based metabolomics. Following the application of BMDExpress2 software, 2903 endogenous metabolic features yielded viable dose-response models, confirming a perturbation to the liver metabolome. Metabolic BMD estimates were similarly sensitive to transcriptional BMDs, and more sensitive than both clinical chemistry and apical end point BMDs. Pathway analysis of the multiomics data sets revealed a major effect of TPhP exposure on cholesterol (and downstream) pathways, consistent with clinical chemistry measurements. Additionally, the transcriptomics data indicated that TPhP activated xenobiotic metabolism pathways, which was confirmed by using the underexploited capability of metabolomics to detect xenobiotic-related compounds. Eleven biotransformation products of TPhP were discovered, and their levels were highly correlated with multiple xenobiotic metabolism genes. This work provides a case study showing how metabolomics and transcriptomics can estimate mechanistically anchored points-of-departure. Furthermore, the study demonstrates how metabolomics can also discover biotransformation products, which could be of value within a regulatory setting, for example, as an enhancement of OECD Test Guideline 417 (toxicokinetics).PMID:38842447 | DOI:10.1021/acs.chemrestox.4c00002

Eur Heart J. 2024 Jun 6:ehae244. doi: 10.1093/eurheartj/ehae244. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.METHODS: Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10).RESULTS: In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12-2.21), P < .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects.CONCLUSIONS: Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.PMID:38842092 | DOI:10.1093/eurheartj/ehae244

Curr Opin Crit Care. 2024 May 29. doi: 10.1097/MCC.0000000000001169. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: To discuss future research themes and study design in cardiogenic shock.RECENT FINDINGS: Cardiogenic shock research faces multiple challenges, hindering progress in understanding and treating this life-threatening condition. Cardiogenic shock's heterogeneous nature poses challenges in patient selection for clinical trials, potentially leading to variability in treatment responses and outcomes. Ethical considerations arise due to the acuity and severity of the condition, posing challenges in obtaining informed consent and conducting randomized controlled trials where time to treatment is pivotal.SUMMARY: This review discusses research in this area focusing on the importance of phenotyping patients with cardiogenic shock, based on artificial intelligence, machine learning, and unravel new molecular mechanisms using proteomics and metabolomics. Further, the future research focus in mechanical circulatory support and targeting inflammation is reviewed. Finally, newer trial designs including adaptive platform trials are discussed.PMID:38841905 | DOI:10.1097/MCC.0000000000001169

Microbiome Res Rep. 2024 Mar 13;3(2):21. doi: 10.20517/mrr.2023.76. eCollection 2024.ABSTRACTAim: Non-salt Suancai is an acidic fermented vegetable consumed by the Chinese Yi ethnic group. Traditionally, it is produced by fermentation without salt in a cold environment. The present study aimed to investigate the metabolite and microbial characteristics, and the effects of substrates/suppliers ingredients on non-salt Suancai. Methods: A simulated fermentation system of non-salt Suancai was constructed by using different substrates/suppliers' ingredients. The coherence and differential detection of the metabolite and microbial characteristics were done through non-target metabolomic and metagenomic analysis. Results: Lactic acid was the predominant organic acid across all samples. The enumeration of the Lactic acid bacteria showed no discernible differences between study groups, but that of yeast was highest in the mustard leaf stem (Brassica juncea var. latipa). The three major biological metabolic pathways were metabolism, environmental information, and genetic information processing based on the KEGG database. The metabolite diversity varied with the substrate/supplier of ingredients based on the PLS-DA plot. Lactiplantibacillus, Leuconostoc, and Lactococcus were prevalent in all samples but differentially. The microbial diversity and richness varied significantly, with 36~291 species being identified. Among the various substrates collected from the same supplier, 29, 59, and 29 differential species were identified based on LEfSe [linear discriminant analysis (LDA) > 2, P < 0.05]. Leuconostoc citreum, Leuconostoc mesenteroides, Leuconostoc pseudomesenteroides, Lactiplantibacillus plantarum, and Leuconostoc lactis were likely to be used as the species to discriminate samples collected from different suppliers. Conclusions: This research contributed to the exploration of microbial and metabolite characteristics behind the ingredient restriction of non-salt Suancai using traditional technology.PMID:38841414 | PMC:PMC11149085 | DOI:10.20517/mrr.2023.76

Microbiome Res Rep. 2024 Jan 18;3(2):14. doi: 10.20517/mrr.2023.65. eCollection 2024.ABSTRACTThe intestinal microbiota and its metabolites are known to influence host metabolic health. However, little is known about the role of specific microbes. In this work, we used the minimal consortium Oligo-Mouse-Microbiota (OMM12) to study the function of Coriobacteriia under defined conditions in gnotobiotic mice. OMM12 mice with or without the addition of the dominant gut bacterium Eggerthella lenta (E. lenta) were fed with diets varying in fat content and primary bile acids. E. lenta stably colonised the mouse caecum at high relative abundances (median: 27.5%). This was accompanied by decreased occurrence of Akkermansia muciniphila and Enterococcus faecalis, but results did not reach statistical significance in all groups depending on diet and inter-individual differences. Changes in host parameters (anthropometry, blood glucose, and cholesterol) and liver proteomes were primarily due to diet. In contrast, metabolomes in colon content differed significantly between the colonisation groups. The presence of E. lenta was associated with elevated levels of latifolicinin C acid and decreased creatine, sarcosine, N,N-dimethylarginine, and N-Acetyl-DL-methionine. In conclusion, E. lenta altered specific metabolites in the colon but did not have significant effects on the mice or liver proteomes under the conditions tested due to marked inter-individual differences.PMID:38841406 | PMC:PMC11149096 | DOI:10.20517/mrr.2023.65

Front Microbiol. 2024 May 22;15:1365254. doi: 10.3389/fmicb.2024.1365254. eCollection 2024.ABSTRACTINTRODUCTION: The efficient utilization of straw resources as animal feed has gained considerable attention. The objective of this study was to evaluate whether Lentinus sajor-caju treatment alters the chemical composition and antioxidant activity of highland barley straw and enhances its functional value as a ruminant feed.METHODS: The chemical composition, antioxidant capacity, and metabolomic profile of highland barley straw were determined after 21 days of solid-state fermentation with L. sajor-caju at 25°C. The differential metabolites between fermented and unfermented highland barley straw were identified by LC-MS and the relationship between the identified metabolites and antioxidant capacity was elucidated.RESULTS: The results showed that, compared with untreated highland barley straw, the crude protein and ether extract contents were higher (51.55 and 76.43%, respectively) in highland barley straw after 21 days of incubation with L. sajor-caju, whereas the hemicellulose, cellulose, and acid detergent lignin contents were lower (2.48, 25.08, and 45%, respectively). The total antioxidant capacity was significantly higher in L. sajor-caju-treated than in untreated highland barley straw. In total, 600 differential metabolites (301 upregulated and 299 downregulated) were identified between L. sajor-caju-fermented and unfermented highland barley straw. Correlation analysis results showed that Fe2+ scavenging and total phenolic content were strongly correlated with total antioxidant capacity. Meanwhile, the differential flavonoid metabolites between fermented and unfermented highland barley straw were primarily associated with antioxidant activity, with kaempferol 3-xylosylglucoside, isoginkgetin, and rhoifolin being the most representative.CONCLUSION: Thus, this study demonstrates that L. sajor-caju could enhance the functional value of highland barley straw, showing the potential of L. sajor-caju for improving the utilization of agricultural straws in ruminants.PMID:38841071 | PMC:PMC11150714 | DOI:10.3389/fmicb.2024.1365254

Hortic Res. 2024 Feb 17;11(6):uhae093. doi: 10.1093/hr/uhae093. eCollection 2024 Jun.ABSTRACTThe white water lily (Nymphaea candida), exemplifying nature's resilience, thrives in the high-altitude terrains of Xinjiang, China, serving as an ideal model for investigating cold adaptation mechanisms in aquatic plants. This study meticulously elucidates the complex cold adaptation mechanisms of the white water lily through a comprehensive and integrated methodological approach. We discovered that the water lily undergoes ecodormancy in winter, retaining high cellular viability and growth potential. During overwintering, the white water lily demonstrates effective resource reallocation, a process facilitated by morphological adjustments, thereby strengthening its resistance to cold temperatures. This enhancement is achieved particularly through the compartmentalization of large vacuoles, the accumulation of osmoregulatory substances, and an increased antioxidant capacity. We established the first exhaustive full-length transcriptome for the white water lily. A subsequent comprehensive analysis of the transcriptome, phytohormones, and metabolome uncovered a multifaceted regulatory network orchestrating cold adaptation. Our research spotlights phytohormone signaling, amino acid metabolism, and circadian rhythms as key elements in the water lily's defense against cold. The results emphasize the critical role of nitrogen metabolism, especially amino acid-related pathways, during cold stress. Metabolite profiling revealed the importance of compounds like myo-inositol and L-proline in enhancing cold tolerance. Remarkably, our study demonstrates that the white water lily notably diminishes the utilization of unsaturated fatty acids in its temperature regulation strategies. In conclusion, this research substantially enriches our understanding of the white water lily's intricate cold adaptation mechanisms, offering new perspectives on the adaptive strategies of aquatic plants and potential applications in agricultural advancement.PMID:38840939 | PMC:PMC11151331 | DOI:10.1093/hr/uhae093

iScience. 2024 Apr 10;27(6):109711. doi: 10.1016/j.isci.2024.109711. eCollection 2024 Jun 21.ABSTRACTObesity, characterized by enlarged and dysfunctional adipose tissue, is among today's most pressing global public health challenges with continuously increasing prevalence. Despite the importance of post-translational protein modifications (PTMs) in cellular signaling, knowledge of their impact on adipogenesis remains limited. Here, we studied the temporal dynamics of transcriptome, proteome, central carbon metabolites, and the acetyl- and phosphoproteome during adipogenesis using LC-MS/MS combined with PTM enrichment strategies on human (SGBS) and mouse (3T3-L1) adipocyte models. Both cell lines exhibited unique PTM profiles during adipogenesis, with acetylated proteins being enriched for central energy metabolism, while phosphorylated proteins related to insulin signaling and organization of cellular structures. As candidates with strong correlation to the adipogenesis timeline we identified CD44 and the acetylation sites FASN_K673 and IDH_K272. While results generally aligned between SGBS and 3T3-L1 cells, details appeared cell line specific. Our datasets on SGBS and 3T3-L1 adipogenesis dynamics are accessible for further mining.PMID:38840842 | PMC:PMC11152682 | DOI:10.1016/j.isci.2024.109711

Mol Nutr Food Res. 2024 Jun 5:e2400004. doi: 10.1002/mnfr.202400004. Online ahead of print.ABSTRACTFatigue, a common symptom in both diseased and healthy individuals, is a biological phenomenon characterized by a sense of extreme physical or mental exhaustion. To explore novel drugs and food sources of anti-fatigue, the hydroalcoholic extract of the root of Mirabilis himalaica (MH extract) is evaluated as anti-fatigue agents in this work, and clarifies that the mechanism of MH intervention in fatigue symptoms, and distribution of the anti-fatigue constituents in the plant of Mirabilis himalaica is examined. The results show that the MH extract have a significantly anti-fatigue effect via the pharmacological experiment and biochemical indicators. The network pharmacology, metabolomics, molecular docking, and pharmacology are integrated to determine that boeravinone A, B, and E are the pharmacoperones of anti-fatigue. Moreover, the compounds of boeravinone are present only in the root and not in the leaf and stem of the Mirabilis himalaica, which validates that root of Mirabilis himalaica is historically and officially utilized medicinal parts.PMID:38840434 | DOI:10.1002/mnfr.202400004

J Mass Spectrom. 2024 Jul;59(7):e5042. doi: 10.1002/jms.5042.NO ABSTRACTPMID:38840330 | DOI:10.1002/jms.5042

Proc Jpn Acad Ser B Phys Biol Sci. 2024 Jun 5. doi: 10.2183/pjab.pjab.100.023. Online ahead of print.ABSTRACTTardigrades are microscopic animals that are renowned for their capabilities of tolerating near-complete desiccation by entering an ametabolic state called anhydrobiosis. However, many species also show high tolerance against radiation in the active state as well, suggesting cross-tolerance via the anhydrobiosis mechanism. Previous studies utilized indirect DNA damaging agents to identify core components of the cross-tolerance machinery in species with high anhydrobiosis capacities. However, it was difficult to distinguish whether transcriptomic changes were specific to DNA damage or mutual with anhydrobiosis. To this end, we performed transcriptome analysis on bleomycin-exposed Hypsibius exemplaris. We observed induction of several tardigrade-specific gene families, including a previously identified novel anti-oxidative stress family, which may be a core component of the cross-tolerance mechanism. We also identified enrichment of the tryptophan metabolism pathway, for which metabolomic analysis suggested engagement of this pathway in stress tolerance. These results provide several candidates for the core component of cross-tolerance, as well as possible anhydrobiosis machinery.PMID:38839369 | DOI:10.2183/pjab.pjab.100.023